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Autoimmune Testing, Diagnosis, and Treatment in Neurology Sarah Sullivan, DO Northwest NeuroSpecialists Medical Director, NWMC Stroke Center
Autoimmune Testing,
Diagnosis, and
Treatment in Neurology
Sarah Sullivan, DO
Northwest NeuroSpecialists
Medical Director, NWMC Stroke Center
Autoimmune Diseases of the Nervous System
Guillain-Barre Syndrome
Inflammatory Myopathy
Multiple Sclerosis
Multifocal Motor Neuropathy
Myasthenia Gravis/LEMS
NMO
OMS
PANDAS
Paraneoplastic Nervous System Disorders
Stiffman Syndrome
Stroke (Antiphospholipid Antibody Syndrome)
Transverse Myelitis
Guillain-Barre: FeaturesEponym for heterogeneous group of acute immune-mediated PN; multiple variants
Presentation: Ascending, symmetric paralysis/paresthesias with autonomic dysfxn risk
98% plateau at 4 weeks
1-3/100,000 persons annually
Peaks in young adulthood (C.jejuni and CMV) and elderly (?failing immunosuppressor mechanisms)
Guillain-Barre: Testing
Physical Exam
Lumbar puncture
Electrodiagnostic studies
Guillain-Barre: Diagnosis
• Relative symmetry of symptoms
• Mild sensory symptoms or signs
• Cranial nerve involvement, especially bilateral weakness of facial muscles
• Recovery beginning two to four weeks after progression ceases
• Autonomic dysfunction
• Absence of fever at onset
• High concentration of protein in cerebrospinal fluid, with fewer than 10 cells per cubic millimeter
• Typical electrodiagnostic features
• Features excluding diagnosis
• Diagnosis of botulism, myasthenia, poliomyelitis, or toxic neuropathy
• Abnormal porphyrin metabolism
• Recent diphtheria
• Purely sensory syndrome, without weakness
Guillain-Barre:Diagnosis
Antecedent events in 2/3 pts (CMV, C-jejuni, HIV, EBV, VZV)
Influenza vaccine - Studies in 1992-1993 and 1993-1994 flu seasons; CDC Vaccine Adverse Event Reporting System - 2003 surveillance
summary “the risk of developing vaccine-assoc GBS is less than the risk of severe influenza”
Guillain-Barre: Diagnosis
The following groups should not receive the flu shot (TIV):
• People who have ever had a severe allergic reaction to influenza vaccine.
• People with a history of Guillain-Barré Syndrome (a severe paralytic illness, also called GBS) that occurred after receiving influenza vaccine and who are not at risk for severe illness from influenza should generally not receive vaccine. Tell your doctor if you ever had Guillain-Barré Syndrome. Your doctor will help you decide whether the vaccine is recommended for you.
Guillain-Barre: TreatmentEarly intubation: hypoxia, weak cough, aspiration, FVC < 15mL/kg or reduction of >30% of FVC
30% of pts (Hahn AF, Lancet 1998).
Autonomic monitoring: HR/BP/Arrythmias -atropine, short-acting agents (nitroprusside); IV fluids and supine positioning, temporary pacing the
2nd/3rd degree heart block
DVT prophylaxis
ICU admit: labile dysautonomia, FVC < 20mL/kg, severe bulbar palsy (Hughes RA, Arch Neurology, Aug 2005)
Guillain-Barre:TreatmentOnly two therapies proven effective (Hughes RA, et al. Neurology. 2003).
PE - 5 PE over 5-10 days
IVIG - 400mg/kg/day for 5 days; start w/in 4 wks of sx onset
Thought to dec autoantibody production/increase solubilization/removal of immune complexes
Shorted recovery time by 50%
Combining neither improves outcome/shortens duration (Hughes, et al. Neurology, Sept 2003)
Guillain-Barre: Treatment
Guillain-Barre: Treatment
Corticosteroids - ineffective alone/ with IVIG may
hasten recovery without impact on long-term (Hughes,
Cochrane, Apr 2006).
IV eculizumab (prevents reps paralysis in animals) (Pritchard J, Neurology, Nov 2003).
Mycophenolate mofetil with IVIG - no benefit (Garssen MP, J
Neurol Neurosurg Psychiatry. Sep 2007).
Guillain-Barre: Treatment
Pain management: gabapentin, carbmazepine,
TCAs, tramadol; avoid narcotics (ileus)
Manage psychologic stress
Guillain-Barre: PrognosisProlonged intubation/ICU management;
2-12% mortality (Bersano A, J Neurol. 2006)
Long-term residual PN (medium-/large-sized myelinated fibers) (Dornonville de la Cour C, Neurology. Jan 2005)
Poorer prognosis: female, >57yo, LOS > 11dys, ICU tx, D/C to rehab (Khan, et al. J. Neurol. Jul 2010)
Not correlative with severity at onset
85% pts full/fxnal recovery in 6-12 mos.; maximal
at 18 mos
Myasthenia Gravis: Features
Autoimmune d/o of ab formation against
Ach nicotinic postsynaptic receptors at
the NMJxn of skeletal mm
Ocular/generalized
EOM 50% initially; 90% during the
course
Increased by exertion/alleviated by rest
87% have generalized dz within 13
months after onset
20/100,000 individuals
MYASTHENIA GRAVIS FOUNDATION
Myasthenia Gravis: TestingLabs: 67% positive (generalized), 44% (ocular)
False positives: thymoma, LEMS, small cell lung
CA, RA with penicillamine, 1-3% of pop >70 yo
Chest CT/XR for thymoma; MRI for ocular MG;
Electrodx studies
Ice test
Tensilon test
Myasthenia Gravis: Diagnosis
http://emedicine.medscape.com/article/1171206-overview
Myasthenia Gravis: Diagnosis
No formal diagnostic criteria established
Classification System
Class I - ocular
Class II - Mild weakness other than ocular
Class III - Mod weakness other than ocular
Class IV - Severe weakness
Class V - Intubation
Myasthenia Gravis: Treatment
Monitor for rapid resp decline
Hypoxemia; CO2 retention; poor resp effort
Monitor for initial deterioration
Myasthenia Gravis: TreatmentAchE inhibitors - initial tx for mild MG
Immunomodulating agents - Corticosteroids, azathioprine, cyclosporine A, methotrexate/cyclophosphamide
IVIg - moderate/severe MG worsening into crisis; elderly; complex comorbid dz
PE - myasthenic crisis; prep for sx; improvement in couple days, doesn’t last for more than 2 months
Thymectomy - all pts with thymoma and pt’s age 10-55 without thymoma but with gen MG; delay in ocular
Myasthenia Gravis: Treatment
Myasthenia gravis:Treatment
Myasthenia Gravis: Prognosis
3-4% mortality (aspiration - pneumonia, falls, med complications)
Risk factors: age >40, thymoma, short history of progressive disease
LEMS
Pre-synaptic disorder
Autoimmune response against the VGCCs on the pre-synaptic motor nerve terminal
Associated SCLC - 1%
Other Paraneoplastic Syndromes
Subacute cerebellar ataxia
Limbic encephalitis
Opsoclonus-myoclonus
Stiff-Person syndrome
The End
References
Saguil, Aaron. “Evaluation of the Patient with
Muscle Weakness.” American Family Physician. 2005 Apr 1: 71 (7): 1327-1336.
Newswanger, Dana, et al. “Guillain-Barre Syndrome” American Family Physician. 2004 May 15; 69 (10): 2405-2410.
